Current evidence suggests that host defense against gonococci involves polymorphonuclear neutrophils (PMN) which respond by migration to the site of infection (chemotaxis), adherence to and ingestion of gonococci (phagocytosis), and intracellular killing of the organisms. Serum factors (antibody, complement) participate through the formation of chemotactic factors and opsonins and by direct bacteriolysis. Gonococci possess virulence factors which allow them to evade these defense mechanisms and are thus important determinants in the pathogenesis of different clinical syndromes of gonorrhea. Virulent gonococci exhibit attachment to PMN but resist ingestion and killing, whereas avirulent organisms are internalized and killed. Organisms isolated from patients with disseminated gonococcal infection (DGI) tend to be resistant to the bactericidal activity of serum, whereas strains causing symptomatic local infection are generally serum-sensitive. Asymptomatic urethritis which is characterized by a limited influx of PMN is caused by gonococci which are similar to DGI strains. We propose a multifaceted series of studies, building on the experience of our laboratory in dealing with gonococci, PMN and complement. The emphasis will be on comparisons of gonococci isolated from patients with different clinical syndromes. The ability of gonococci to elicit chemotaxis will be investigated using human PMN in Boyden chambers. Attachment and ingestion of gonococci will be examined in experiments using radiolabeled organisms as well as histochemical and microscopic techniques. The ability of gonococci to stimulate PMN degranulation and metabolic activity will be determined by measurements of enzyme release and oxidative events. Microbicidal activity of PMN against gonococci will be characterized by using cell-free systems (e.g., myeloperoxidase-H2O2-halide) and intact human PMN, emphasizing extracellular vs. intracellular killing. Antibody and complement mediated opsonization and bacteriolysis will be studied using immune serum and serum deficient in C8 or gammaglobulins. This approach will provide valuable new information about the pathogenesis of gonococcal infections and will have broader implications relating to the basic biology of PMN interactions with microorganisms.